Pharmaceutical compositions and medicaments typically are orally ingested in liquid, tablet, and capsule form. The capsule form of medication is considered to many to be a preferred form of dosage since the recepient users perceive them as having no aftertaste, being easy to swallow, causing no indigestion, and working quickly. Such capsules generally consist of a hard shell composed of two prefabricated cylindrical parts (a cap and a body), one end of each of which is rounded and closed, and the other end of which is open. A medicament or medicaments, usually in paste, liquid, or powder form, are filled into the body which is then joined with a cap to close the capsules. The hard shell capsules generally are made of gelatin or other materials whose properties are pharmaceutically acceptable.
The standard gelatin capsule in which the side wall of the body of the capsule is telescopically received within the smooth cylindrical side wall of the cap can be readily re-opened after filling, providing the possibility of contamination by insertion of other materials which may be harmful or undesirable for ingestion. One solution to prevent re-opening of capsules after filling has been to band the joined cap and body of each capsule at their seam of overlap with a gelatin band or film. This involves contact of each capsule by a liquid gelatin-coated roller to apply the band thereto. As an alternative to capsule banding, the smooth side walls of the cap and body of the capsules have been shape-modified by provision of mating circular grooves and ridges to achieve a "snap-fit" securement of the cap and body resistant to re-opening of the same. Capsules having structurally modified cap and body wall configurations are commercially available and sold by Capsugel division of Warner-Lambert Corporation under the trademarks Snap-Fit.TM., Coni-Snap.TM., and Coni-Snap Supro.TM..
While such shape-modified cap and body structures provide better securement and make the capsules more difficult to open after joining, tamper-resistance and security of medicinal capsules may be further improved by sealing the overlapping walls of the caps and the bodies after filling. Several techniques have been employed for sealing of hard gelatin capsules, including wetting the overlapping contiguous faces of the cap and body side walls of the filled capsules with a special melting-point-lowering liquid which is believed to act to dissolve the amorphous part of the gelatin between the overlapped side walls, lower the glass transition temperature of the gelatin, and depress the melting-point of the crystalline part of the gelatin. The wetted capsules are then thermally treated to cause final heat-sealing and bonding of their overlapped side wall portions.
Such wetting liquids must be readily ingestible, available, and applied to the capsules. A number of wetting liquids and their methods of application to gelatin capsules are disclosed and described in U.S. Pat. No. 4,539,060 to Wittwer et al., and in co-pending U.S. patent application Ser. No. 06/582,364 filed Feb. 22, 1984 and now U.S. Pat. No. 4,656,066. A preferred wetting liquid is a mixture of water and an alcohol, such as ethanol, two solvents which are frequently and commonly used in the manufacture of pharmaceutical products. The selection of the type and ratio of the components of the wetting liquid depends upon the composition of the capsule wall, the type of printing on the capsule, and the amount of thermal energy to be applied during final heat-sealing of the cap and body walls to prevent their being opened after sealing without destruction of the capsule itself.
The most effective sealing of capsules is believed achieved by using a sealing fluid placed within the area of the capsule side walls defined by the overlapping contiguous cap and body side wall, followed by thermal treatment to effect a final bonding of the cap and body side walls. One commercially available method for sealing hard gelatin capsules so that they cannot be opened without visible destruction is known as the Licaps.TM. capsule-sealing process developed by Capsugel. This process involves wetting the wall contact area between the cap and body with a melting-point-lowering liquid, such as ethanol and water. If the capsules are wetted by immersion in the wetting liquid to cause the flow of the wetting liquid between the contiguous side walls of the cap and body by capillary action, excess wetting liquid must be removed from the outer walls of the capsule in suitable manner, as by air-drying or mechanical agitation, to avoid possible damage to the capsule in subsequent heat-treating operations. After removal of the excess wetting liquid, the cap and body sections are then thermally sealed into one capsule unit.
Aforesaid U.S. Pat. No. 4,539,060 discloses various apparatus for wetting, drying, and thermally sealing gelatin capsules. Certain of the apparatus consists of a continuous conveyor having net or wire mesh baskets into which capsules are ejected from a capsule-filling machine. The capsules are randomly oriented in the baskets which are dipped into a tank of sealing fluid to place the wetting liquid in the overlapped portion of the cap and body side walls by capillary action. Thereafter, the capsules are conveyed through a drying stream of conditioned air from a blower to remove excess sealing fluid from the surface of the capsules to avoid deformation and sticking of the capsules during subsequent thermal treatment. The surface-dried capsules are then heated by a specific source and quantity of thermal energy, such as in a kiln, an oven, or hot-air dryer.
Another apparatus for drying and thermal treatment of wetted capsules to seal the same is a conveying and heating apparatus sold by Glatt GmbH with offices at D-7851 Birozer, Germany BRD. This apparatus consists of combined stations for wetting, draining off or drying of excess wetting agent, and thermally sealing the dried-off capsules. The capsules, after spraying or immersion to wet the same, are conveyed by a helical or screw-type conveyor through a porous or mesh passageway as excess wetting liquid is drained from the capsules. The capsules, after draining, are alternately fed from the draining-off device to parallel-arranged, fluidized bed dryers. The two dryers are alternately programmed to first dry a batch amount of collected capsules by passage of air therethrough, and thereafter subject the dried capsules to heated air to impart thermal energy to the capsules sufficient to produce final of the overlapped side walls of the caps and bodies thereof.
The sealing machine alternatively may comprise a rotating conical wire mesh basket in which a wetting liquid is sprayed on the entire outer surface of the capsules as they are continuously fed therethrough. Capillary action causes transfer of some of the wetting liquid to the area between the overlapped side walls of the cap and body of each capsules. Excess wetting liquid is removed from the capsules as they approach the exit end of the basket, both by mechanical drainage and application of room-temperature air. From the liquid applicator basket, the capsules are then directed alternately, in batchwise manner, to the two drying and sealing chambers in the form of fluidized beds. Since two chambers are available, the sealing machine operates to fill the chambers in alternating fashion, so that conditioned cool air is first passed through each chamber during capsule-filling to further dry the capsules, while heated air is thereafter passed through each chamber after it is filled to thermally seal the capsules. The excess wetting liquid, generally comprising a mixture of water and alcohol, is thus removed from the capsules by drainage and evaporation and may be eventually collected and processed by special recovery equipment to meet environmental regulations and requirements for disposal.
If metered amounts of the wetting liquid are selectively applied to the overlapping wall contact areas of the cap and body portions of the capsules, as by spraying the liquid against the capsule side wall adjacent the seam of the body and cap portions, the use of and removal of excess wetting liquid from the outer wall surface of the capsule may be avoided. In such cases, the capsules may be immediately subjected to thermal treatment for final heat seal of the capsule without drying. Metered spraying to apply to wetting liquid is disclosed and described in the aforesaid U.S. Pat. No. 4,539,060 and the referred to co-pending U.S. patent application commonly owned with the present application.
In commercial manufacture of hard gelatin medicinal capsules, it is obviously desirable to fill, close, and seal the capsules containing medicaments in a continuous, economical, and expedient manner. As such, it is desirable to fill, close, and thermally treat the capsules in a continuous operation.